Biophysical regulation of epigenetic state and cell reprogramming
TL;DR: It is shown that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency and promote a mesenchymal-to-epithelial transition in adult fibroblasts.
Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells biochemically through the expression of a few transcription factors. It is now shown that aligned microgrooves or nanofibres on cell-adhesive substrates can promote the reprogramming of somatic cells more efficiently through epigenetic regulation of genes related to pluripotency and the mesenchymal-to-epithelial transition. The findings suggest that the epigenetic state can be regulated by variations in cell morphology.
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TL;DR: How cell adhesions interact with nanotopography is discussed, and insight is provided as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled.
Abstract: Stem cells respond to nanoscale surface features, with changes in cell growth and differentiation mediated by alterations in cell adhesion. The interaction of nanotopographical features with integrin receptors in the cells' focal adhesions alters how the cells adhere to materials surfaces, and defines cell fate through changes in both cell biochemistry and cell morphology. In this Review, we discuss how cell adhesions interact with nanotopography, and we provide insight as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled. We expect knowledge gained from the study of cell-nanotopography interactions to accelerate the development of next-generation stem cell culture materials and implant interfaces, and to fuel discovery of stem cell therapeutics to support regenerative therapies.
879 citations
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...integral role in embryonic tissue morphogenesis [114, 121]....
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TL;DR: Recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions are discussed, and a subset of the operative signal transduction mechanisms that have begun to emerge are overviewed.
Abstract: The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine.
787 citations
TL;DR: The focus of this review is to compare the advantages and disadvantages of these methods in terms of their ability to retain desired ECM characteristics for particular tissues and organs.
Abstract: As the gap between donors and patients in need of an organ transplant continues to widen, research in regenerative medicine seeks to provide alternative strategies for treatment. One of the most promising techniques for tissue and organ regeneration is decellularization, in which the extracellular matrix (ECM) is isolated from its native cells and genetic material in order to produce a natural scaffold. The ECM, which ideally retains its inherent structural, biochemical, and biomechanical cues, can then be recellularized to produce a functional tissue or organ. While decellularization can be accomplished using chemical and enzymatic, physical, or combinative methods, each strategy has both benefits and drawbacks. The focus of this review is to compare the advantages and disadvantages of these methods in terms of their ability to retain desired ECM characteristics for particular tissues and organs. Additionally, a few applications of constructs engineered using decellularized cell sheets, tissues, and whole organs are discussed.
463 citations
TL;DR: Two biomaterials approaches to control the regenerative capacity of the body for tissue-specific regeneration by modulating the extracellular microenvironment or driving cellular reprogramming are outlined.
Abstract: In situ tissue regeneration harnesses the body’s regenerative potential to control cell functions for tissue repair. The design of biomaterials for in situ tissue engineering requires precise control over biophysical and biochemical cues to direct endogenous cells to the site of injury. These cues are required to induce regeneration by modulating the extracellular microenvironment or driving cellular reprogramming. In this Review, we outline two biomaterials approaches to control the regenerative capacity of the body for tissue-specific regeneration. The first approach includes the use of bioresponsive materials with an ability to direct endogenous cells, including immune cells and progenitor or stem cells, to facilitate tissue healing, integration and regeneration. The second approach focuses on in situ cellular reprogramming via delivery of transcription factors, RNA-based therapeutics, in vivo gene editing and biomaterials-driven epigenetic transformation. In addition, we highlight tools for engineering the next generation of biomaterials to modulate in situ tissue regeneration. Overall, leveraging the regenerative potential of the human body via engineered biomaterials is a simple and effective approach to replace injured or diseased tissues. In situ tissue regeneration harnesses the body’s regenerative potential for tissue repair using engineered biomaterials. In this Review, we outline various biomaterials approaches to control the body’s regenerative capacity for tissue-specific regeneration by modulating the extracellular microenvironment or driving cellular reprogramming.
325 citations
TL;DR: Stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon, so bioengineering technologies are poised to overcome current bottlenecks and revolutionize the field of regenerative medicine.
Abstract: Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical properties can preserve stem cell function in culture, enhance survival of transplanted cells and guide tissue regeneration. Rapid progress with three-dimensional hydrogel culture platforms provides the opportunity to grow patient-specific organoids, and has led to the discovery of drugs that stimulate endogenous tissue-specific stem cells and enabled screens for drugs to treat disease. Therefore, bioengineering technologies are poised to overcome current bottlenecks and revolutionize the field of regenerative medicine.
284 citations
References
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TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
23,959 citations
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
12,204 citations
TL;DR: This article showed that OCT4, SOX2, NANOG, and LIN28 factors are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.
Abstract: Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers. Such induced pluripotent human cell lines should be useful in the production of new disease models and in drug development, as well as for applications in transplantation medicine, once technical limitations (for example, mutation through viral integration) are eliminated.
9,836 citations
TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.
3,995 citations
01 Jan 2007
TL;DR: Yu et al. as discussed by the authors proposed online material for induced pluripotent stem cell lines derived from human Somatic Cells, which can be used for transplanting human stem cells to humans.
Abstract: Supporting Online Material for Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells Junying Yu,* Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L. Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, James A. Thomson* *To whom correspondence should be addressed. E-mail: jyu@primate.wisc.edu (J.Y.); thomson@primate.wisc.edu (J.A.T.)
3,632 citations